Background PP-007 is a PEGylated bovine carboxyhemoglobin gas transfer molecule with pleotropic cytoprotective effects, vasodilatation, plasma expansion and optimization of oxygen delivery. Rodent middle cerebral artery occlusion models have demonstrated that PP-007 increases blood flow in the collateral circulation and reduces final infarct volumes, supporting a potential role as neuroprotective agent in acute ischemic stroke. We aim to evaluate the safety and feasibility of PP-007 as an adjunctive treatment to mechanical thrombectomy (MT) in patients with stroke secondary to large vessel occlusion (LVO).
Methods HEMERA-1 was a multicenter, prospective, randomized, controlled phase 1 clinical trial. Anterior circulation LVO patients were assigned in a 3:1 ratio to receive either PP-007 (320mg/kg: 30 minutes bolus followed by 2-hour infusion) plus MT or MT alone within 24 hours after symptom onset. Other key inclusion criteria were baseline NIHSS ≥6, baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥5 and/or estimated core volumes ≤70mL with mismatch >50mL on CT perfusion, pre-morbid modified Rankin Scale <2, and ineligibility for intravenous thrombolysis. The primary endpoint comprised a comprehensive safety evaluation by a Data Monitoring Safety Board.
Results A total of 17 patients were recruited. The mean ± SD age, baseline NIHSS, and ASPECTS were 74.8±12.7 years, 17.3±4.2, and 7.9±1.8, respectively. Twelve patients were randomized PP-007 plus MT, 1 was randomized but not treated, 4 patients were randomized to MT alone. Recanalization of the occluded vessel was achieved in all patients. Seven PP-007 patients in 2 centers had temporary elevation of Partial Prothrombin Time most likely artifactual without any clinical consequences. A transient systolic blood pressure increase (20-40 mmHg) during the bolus was observed in all PP-007 patients without any clinical consequences. There were no other safety concerns.
Conclusion No significant safety concerns were identified for the adjunctive use of PP-007in patients undergoing MT (ClinicalTrials.gov NCT04677777).
Disclosures I. Linfante: 2; C; Penumbra, Stryker, Q’Appel, Cerenovus. 3; C; Penumbra, Stryker, Q’Appel, Cerenovus. 4; C; Prolong Pharmaceuticals, InNeuroCo,Three Rivers, InNeuroFine, Deinde. W. Clark: None. D. Houssen: None. R. Hanel: None. R. Reshi: None. G. Dabus: 4; C; three rivers, InNeuroCo, synchron. R. Jubin: 5; C; Prolong Pharmaceuticals. T. Nguyen: None. J. Grotta: None. R. Wicks: None. M. Pervez: None. M. Cipolla: None. D. Liebeskind: None. R. Nogueira: None.
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